Fear itself

Past experiences in my life have instilled into me a deep dislike of being the center of attention.  Talking about what you love, what you're interested in, is arrogance and conceit -- I learned that lesson early.  Also, protect what you care about, or it'll be ridiculed, demeaned, or taken away.  The result was that even in safe situations, I have always been afraid to open up, and even people I've known for years really hardly know me at all.

The fact that I no longer have to spend my life in a protective crouch has not eradicated that fear.  It's a significant part of why I'm as shy and socially awkward as I am, and why I'm the guy at parties (if I get invited in the first place) who's standing there with a glass of scotch, looking around frantically for a dog to socialize with.  I've tried for years to be okay with graciously accepting compliments when they come, and to open up to others about my interests, but to say it doesn't come naturally to me is a wild understatement.

This all comes up because of some research released last month from scientists at the RIKEN Center for Brain Science in Saitama, Japan.  A team consisting of Ray Luo, Akira Uematsu, Adam Weitemier, Luca Aquili, Jenny Koivumaa, Thomas J.McHugh, and Joshua P. Johansen published a paper in Nature: Communications called "A Dopaminergic Switch for Fear to Safety Transitions," wherein we find out that a single neurotransmitter (dopamine) acting in a single part of the brain (the ventral tegmental area) is apparently responsible for unlearning fear responses.

The authors write:

Exposure therapy, a form of extinction learning, is an important psychological treatment for anxiety disorders such as post-traumatic stress disorder (PTSD).  Extinction of classically conditioned fear responses is a model of exposure therapy.  In the laboratory, animals learn that a sensory stimulus predicts the occurrence of an aversive outcome through fear conditioning.  During extinction, the omission of an expected aversive event signals a transition from fear responding to safety.  To switch from fear responding to extinction learning, a brain system that recognizes when an expected aversive event does not occur is required.  While molecular changes occurring in the ventromedial prefrontal cortex (vmPFC) and amygdala are known to be important for storing and consolidating extinction memories, the brain mechanisms for detecting when an expected aversive event did not occur and fear responses are no longer appropriate are less well understood... 

[Our] findings show that activation of VTA-dopamine neurons during the expected shock omission time period is necessary for normal extinction learning and the upregulation of extinction-related plasticity markers in the vmPFC and amygdala.  Notably, inhibition of VTA-dopamine neurons during the shock period of fear conditioning facilitates learning, suggesting that activity in VTA-dopamine neurons is not simply important for learning in response to any salient event.  These results also reveal that distinct populations of VTA-dopamine neurons... are important for the formation of stable, long-term extinction memories.

Team leader Joshua Johansen was unequivocal about the potential for this research in treating long-term anxiety and PTSD.  "Pharmacologically targeting the dopamine system will likely be an effective therapy for psychiatric conditions such as anxiety disorders when combined with clinically proven behavioral treatments such as exposure therapy," he said in a press release from RIKEN.  "In order to provide effective, mechanism-based treatments for these conditions, future pre-clinical work will need to use molecular strategies that can separately target these distinct dopamine cell populations."

Illustration from Charles Darwin's Expression of the Emotions in Man and Animals (1872), captioned, "Terror, from a photograph by Dr. Duchenne."  [Image is in the Public Domain]

I have suffered from serious anxiety most of my life, and I have a dear friend who has PTSD, and believe me -- this is welcome news.  My one attempt to use an anxiolytic medication was a failure (it killed my appetite, which someone with as fast a metabolism as I have definitely doesn't need), and "exposure therapy" has, all in all, been a failure.  The idea that there could be a way to approach these debilitating conditions by targeting a specific molecule in a specific part of the brain is pretty earthshattering.

I know it's a long way between identifying the brain pathway involved in a disorder and finding a way to alter what it's doing, but this is a significant first step.  The idea that I might one day be able to go to social gatherings without feeling a sense of dread, and to talk to people rather than just dogs, is kind of amazing.  Until that happens, I'm probably still going to have to deal with my anxiety, but it's nice to know someone is working on the problem.

************************************

This week's book recommendation is especially for people who are fond of historical whodunnits; The Ghost Map by Steven Johnson.  It chronicles the attempts by Dr. John Snow to find the cause of, and stop, the horrifying cholera epidemic in London in 1854.

London of the mid-nineteenth century was an awful place.  It was filled with crashing poverty, and the lack of any kind of sanitation made it reeking, filthy, and disease-ridden.  Then, in the summer of 1854, people in the Broad Street area started coming down with the horrible intestinal disease cholera (if you don't know what cholera does to you, think of a bout of stomach flu bad enough to dehydrate you to death in 24 hours).  And one man thought he knew what was causing it -- and how to put an end to it.

How he did this is nothing short of fascinating, and the way he worked through to a solution a triumph of logic and rationality.  It's a brilliant read for anyone interested in history, medicine, or epidemiology -- or who just want to learn a little bit more about how people lived back in the day.

[If you purchase the book from Amazon using the image/link below, part of the proceeds goes to supporting Skeptophilia!]

A tincture of madness

As a fiction writer, I have an understandable interest in the neuroscience of creativity.  It's a difficult field to study; getting people to be creative while simultaneously scanning their brains can be tricky.

Now, five researchers at Johns Hopkins have been able to do just that.  A recent paper in Nature by
Malinda J. McPherson, Frederick S. Barrett, Monica Lopez-Gonzalez, Patpong Jiradejvong, and Charles J. Limb entitled "Emotional Intent Modulates The Neural Substrates Of Creativity: An fMRI Study of Emotionally Targeted Improvisation in Jazz Musicians" has shown that creativity requires the interaction between several disparate regions of the brain -- including the ones connected with both negative and positive emotions.

What the researchers did is to take twelve jazz pianists and instruct them to improvise a piece based on emotional cues they got from a photograph of a woman with either a happy, neutral, or sad expression.  They then played their piece while in a fMRI machine, thus giving the scientists a view of what was happening in their brains as they created.

The researchers found there was a distinct difference in the patterns of brain activation depending upon the emotional content of the music the pianists were creating.  The authors write:

[T]his study shows that the impulse to create emotionally expressive music may have a basic neural origin: emotion modulates the neural systems involved in creativity, allowing musicians to engage limbic centers of their brain and enter flow states.  The human urge to express emotions through art may derive from these widespread changes in limbic, reward, and prefrontal areas during emotional expression.  Within jazz improvisation, certain emotional states may open musicians to deeper flow states or more robust stimulation of reward centers.  The creative expression of emotion through music may involve more complex mechanisms by which the brain processes emotions, in comparison to perception of emotion alone. 

More darkly, there's long been a supposed connection between being highly creative and being mentally ill.  The list of individuals who were both is a long one. Ernest Hemingway, Georgia O'Keeffe, Hermann Hesse, Maurice Ravel, F. Scott Fitzgerald, Edgar Allen Poe, Jackson Pollock, Cole Porter, Vincent van Gogh, and Robert Schumann all suffered from varying degrees of mental problems, most of them from clinical depression, schizophrenia, or bipolar disorder.  More than one of these spent the last years of life in a mental institution, and more than one committed suicide.

"The only difference between myself and a madman," Salvador Dalí famously quipped, "is that I am not mad."  Two thousand years earlier, the Roman writer Seneca said, "There is no genius without a tincture of madness."

[image courtesy of the Wikimedia Commons]

This, too, has been studied from a neuroscience perspective. A Swedish researcher has demonstrated that Seneca was right; there is a fundamental connection between creativity and mental illness.   Fredrik Ullén, of the Karolinska Institutet of Stockholm, found a significant connection between creativity and the dopamine (pleasure/reward) system in the brain, which is the same system that is implicated in several forms of mental illness, including schizophrenia, obsessive-compulsive disorder, and tendency to addiction.

Ullén administered a test that was designed to measure a subject's capacity for creative thinking -- for developing more than one solution to the same problem, or using non-linear solution methods to arrive at an answer.  He then analyzed the brain activity of the individuals who scored the highest, and found that across the board, they had lower amounts of dopamine receptors in a part of the brain called the thalamus -- one of the main "switchboards" in the higher brain, and responsible for sorting and processing sensory stimuli.

The implication is that creative people don't have as rigid a sorting mechanism as other, less creative people -- that having a built-in deficiency in your relay system may help you to arrive at solutions to problems that others might not have seen.

The connection between the thalamus, creativity, and sorting issues is supported by a different bit of brain research that found that a miswiring of the thalamus is implicated in another bizarre mental disorder, called synesthesia.  In synesthesia, signals from the sensory organs are misrouted to the incorrect interpretive centers in the cerebrum, and an auditory signal (for example) might be received in the visual cortex.  As a result, you would "see sounds."  Other senses can be crosswired, however -- the seminal study of the disorder is described in Richard Cytowic's book, The Man Who Tasted Shapes.

Synesthsia is apparently also much more common among the creative.  Alexander Scriabin, the early 20th century Russian composer, wrote his music as much from how it looked to him as how it sounded.  He describes a sensation of color being overlaid on what he was actually seeing when he heard specific combinations of notes.  The colors were consistent; C# minor, for example, was always green, Eb major always magenta.  And although Alexander Scriabin's synesthesia was perhaps the most intense, he is not the only composer who was synesthetic; the evidence is strong that Liszt, Rimsky-Korsakov, and Olivier Messaien also had this same miswiring.

The study by Ullén seems to point toward connecting these physiological manifestations with the phenomenon of creativity itself.  "Thinking outside the box," Ullén said, "may be facilitated by having a somewhat less intact box."

So the whole thing is, as you might expect, quite complex.  Creativity, apparently, involves not only the interaction between emotional and cognitive regions of the brain, but between separate cognitive and perceptual modules.  The next time someone asks me where I get the ideas for my novels, however, I'm not sure I want to go into all of this.  I'll probably just stick with my tried-and-true response, which is to smile and say, "I was dropped on my head as an infant."